ECE2013 Oral Communications Pituitary & Molecular Endocrinology (6 abstracts)
The consequences of changing endogenous GH/IGF1 levels on carcinogen-induced mammary gland tumorigenesis are dependent on metabolic status in mice
Manuel D Gahete 1, , Jose Córdoba-Chacón 1 , Daniel D Lantvit 4 , Francisco Perez-Jiminez 3 , José López-Miranda 3 , Steven M Swanson 4 , Justo P Castaño 2 , Raúl M Luque 2 & Rhonda D Kineman 1
1Research and Development Division, Jesse Brown Veteran Affairs Medical Center and Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 2Department of Cell Biology, Physiology and Immunology, University of Cordoba, Reina Sofia University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), and CIBER Fisiopatol, Córdoba, Spain; 3Lipid and Atherosclerosis Research Unit, IMIBIC, Reina Sofia University Hospital, University of Cordoba, and CIBERObn, Avda. Menéndez Pidal, Córdoba, Spain; 4Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL, USA.
ESE Young Investigator Award
Introduction: GH and IGF1 are thought to promote breast carcinogenesis as circulating levels of GH/IGF1 are positively correlated with breast cancer risk in epidemiologic studies, and mouse models with developmental GH/IGF1 deficiency or resistance are less susceptible to breast cancer development. However, no studies have shown that high levels of circulating GH/IGF1 can promote mammary tumorigenesis. In this study, two mouse models with elevated or reduced levels of endogenous GH/IGF1 (HiGH and adult-onset GH-deficient (AOiGHD) mice respectively) were used to test the hypothesis that changes in endogenous GH/IGF1 levels can alter the sensitivity of the mammary gland to tumor formation under normal or diet-induced obese conditions.
Methods/design: 8–10-week-old chow-fed HiGH, AOiGHD and their respective controls were treated with DMBA (500 mg/10 g BW) for 5 consecutive weeks and the development and progression of mammary gland tumors monitored for 24-weeks. Additionally, HiGH and control mice were fed a high-fat diet for 4-weeks, treated with DMBA and monitored during 20-weeks.
Results: The number of AOiGHD females that developed mammary gland tumors was reduced compared to controls, where tumor size and multiplicity were also reduced. Unexpectedly, mammary tumor formation was not increased in chow-fed HiGH mice. In fact, there was a non-significant reduction in tumor multiplicity and a significant delay in tumor latency. Moreover, the number of mice that develop large tumors (>1 cm) was reduced in HiGH mice. In marked contrast, diet-induced obese HiGH mice presented reduced tumor latency and increased tumor incidence, size and multiplicity.
Conclusion: Under normal metabolic conditions (chow-diet), reduced endogenous GH/IGF1 levels in adults protect against mammary gland tumor formation, while elevated endogenous GH/IGF1 levels do not hasten tumor formation. However, under excessive caloric intake, elevated endogenous GH/IGF1 levels accelerate mammary gland tumor formation and progression, indicating the ultimate consequences of GH/IGF1 on breast tumors development is dependent on the metabolic status.
Volume 32
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Endocrine Abstracts
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